title: MiRNA-181a regulates adipogenesis by targeting tumor necrosis factor-α (TNF-α) in the porcine model.
abstract: Adipogenesis is tightly regulated by altering gene expression, and TNF-α is a multifunctional cytokine that plays an important role in regulating lipogenesis. MicroRNAs are strong post-transcriptional regulators of cell differentiation. In our previous work, we found high expression of miR-181a in a fat-rich pig breed. Using bioinformatic analysis, miR-181a was identified as a potential regulator of TNF-α. Here, we validated TNF-α as the target of miR-181a by a dual luciferase assay. In response to adipogenesis, a mimic or inhibitor was used to overexpress or reduce miR-181a expression in porcine pre-adipocytes, which were then induced into mature adipocytes. Overexpression of miR-181a accelerated accumulation of lipid droplets, increased the amount of triglycerides, and repressed TNF-α protein expression, while the inhibitor had the opposite effect. At the same time, TNF-alpha rescued the increased lipogenesis by miR181a mimics. Additionally, miR-181a suppression decreased the expression of fatty synthesis associated genes PDE3B (phosphodiesterase 3B), LPL (lipoprotein lipase), PPARγ (proliferator-activated receptor-γ), GLUT1 (glucose transporter), GLUT4, adiponectin and FASN (fatty acid synthase), as well as key lipolytic genes HSL (hormone-sensitive lipase) and ATGL (adipose triglyceride lipase) as revealed by quantitative real-time PCR. Our study provides the first evidence of the role of miR-181a in adipocyte differentiation by regulation of TNF-α, which may became a new therapeutic target for anti-obesity drugs.
authors.affiliation: Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, China ; Fujian Provincial Key Laboratory of Preventive Veterinary Medicine and Biotechnology, College of Life Science, Longyan University, Fujian, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Lizeng
authors.initials: L
authors.lastname: Guan
authors.forename: Qien
authors.initials: Q
authors.lastname: Qi
authors.forename: Gang
authors.initials: G
authors.lastname: Shu
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Jiang
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.forename: Qianyun
authors.initials: Q
authors.lastname: Xi
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases